A specific proteinase 3 activity footprint in α1-antitrypsin deficiency

Autor: Paul R. Newby, Diana Crossley, Helena Crisford, James A. Stockley, Richard A. Mumford, Richard I. Carter, Charlotte E. Bolton, Nicholas S. Hopkinson, Ravi Mahadeva, Michael C. Steiner, Tom M.A. Wilkinson, Elizabeth Sapey, Robert A. Stockley

Publikováno v: ERJ Open Research, Vol 5, Iss 3 (2019)

α1-Antitrypsin (α1-AT) deficiency is a risk factor for emphysema due to tissue damage by serine proteases. Neutrophil elastase (NE) has long been considered the enzyme responsible. However, proteinase 3 (PR3) also produces the pathological features

Externí odkaz: https://doaj.org/article/095479c2e89f446384bb49f27a617158

The course of A alpha Val541 as a proteinase 3 specific neo-epitope after alpha-1-antitrypsin augmentation in severe deficient patients

Autor: Dirk Jan A.R. Moes, Richard A Mumford, Jan Stolk, Pieter S. Hiemstra, Iris G.M. Schouten

Publikováno v: International Journal of Molecular Sciences
Volume 22
Issue 15
International Journal of Molecular Sciences, 22(15). MDPI
International Journal of Molecular Sciences, Vol 22, Iss 8031, p 8031 (2021)

In alpha-1-antitrypsin deficiency (AATD), neutrophil serine proteases such as elastase and proteinase 3 (PR3) are insufficiently inhibited. A previous study in AATD patients showed a higher plasma level of the specific PR3-generated fibrinogen-derive

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc47515c3028e6d18479b968e7ec3993
https://hdl.handle.net/1887/3209147

A -Val360: a marker of neutrophil elastase and COPD disease activity

Autor: Michael J. Ungurs, Richard A Mumford, Richard I Carter, Robert A. Stockley

Publikováno v: European Respiratory Journal. 41:31-38

Forced expiratory volume in 1 s is currently the most widely used marker of chronic obstructive pulmonary disease (COPD) severity; however, it is a poor surrogate of the emphysematous component and the underlying pathophysiological mechanism, and the

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f769b2750bf5158ca634b80b30b8915
https://doi.org/10.1183/09031936.00197411

Heterocycle-substituted proline dipeptides as potent VLA-4 antagonists

Autor: Kelly M. Treonze, Russell B. Lingham, Richard A. Mumford, Kenneth Alves, Benito Munoz, Weichao Chen, Joyce P. James, Jasmine Zunic, Nicholas D. Smith, Thomas S. Reger, Bowei Wang, Michael F. Gardner, Nicholas Stock, Mitchell D. Green, Qian Si

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 20:1173-1176

A variety of N-linked tertiary amines and heteroarylamines were examined at the 4-position of sulfonylated proline dipeptides in order to improve VLA-4 receptor off-rates and overcome the issue of CYP3A4 time-dependent inhibition of ester prodrugs. A

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::418233da95288470cb2c8fbb4c8b2413
https://doi.org/10.1016/j.bmcl.2009.12.009

Discovery of N-{N-[(3-Cyanophenyl)sulfonyl]-4(R)-cyclobutylamino-(l)-prolyl}-4-[(3′,5′-dichloroisonicotinoyl)amino]-(l)-phenylalanine (MK-0668), an Extremely Potent and Orally Active Antagonist of Very Late Antigen-4

Autor: Gerard R. Kieczykowski, Carrie P. Jones, Ping Liu, Junying Wang, Conrad E. Raab, Qian Si, Xinchun Tong, Thomas J. Lanza, Anne Schuelke, Kelly M. Treonze, Richard A. Mumford, Salony Manior, Stella H. Vincent, James V. Pivnichny, Gloria C. Koo, James P. Jewell, William K. Hagmann, Regina W. Wang, Philip Davies, Linus S. Lin, Malcolm MacCoss

Publikováno v: Journal of Medicinal Chemistry. 52:3449-3452

Extremely potent very late antigen-4 (VLA-4) antagonists with picomolar, whole blood activity and slow dissociation rates were discovered by incorporating an amino substituent on the proline fragment of the initial lead structure. This level of poten

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3a2b44376091abb5e0b00c51b9e55a39
https://doi.org/10.1021/jm900257b